Segmented linear ion trap for enhanced ion activation and storage

ABSTRACT

A linear ion trap system includes a linear ion trap having at least two discrete trapping regions for processing ions. An RF electrical potential generator produces two RF waveforms applied to a pair of pole electrodes of the linear ion trap forming a RF trapping field component to trap ions radially. A multi-output DC electrical potential generator produces a first set of multiple DC field components superimposed to the RF trapping field component and distributed across the length of the linear ion trap to control ions axially. A control unit is configured to switch the DC electrical potentials and DC field components collectively forming a first trapping region of the at least two discrete trapping regions that is populated with ions to alter ion potential energy from a first level to a second level, and to enable at least a first ion processing step in at least one of the first and second levels.

RELATED APPLICATION

This application is a continuation of U.S. patent application Ser. No.15/877,475, filed Jan. 23, 2018, which is a continuation of U.S. patentapplication Ser. No. 15/015,101, filed Feb. 3, 2016, now U.S. Pat. No.9,978,578.

BACKGROUND Field of the Invention

The technical field of the invention relates to ion analysis using massspectrometry. More particularly, to the development of a segmentedlinear ion trap to enable an extended range of ion processing techniquesapplied sequentially and facilitated by controlling the RF and DCelectrical potential of trapping regions . Specifically, to thedevelopment of electronics and associated new techniques for ion trapoperation.

Background Information

Linear ion traps have evolved into extremely powerful and versatileanalytical devices and constitute a significant and indispensibleinstrumentation section in modern mass spectrometry. Deployed asstand-alone mass analyzers or integrated in hybrid mass spectrometers,the range of tools and methods available for manipulating gas phase ionsare remarkably wide. Linear ion traps are ideal platforms for developingand testing novel designs to achieve enhanced performance capabilitiesand further extend versatility. Reviews on linear ion trapinstrumentation are concerned with 2-dimensional RF trapping fields andthe properties of radial ion confinement, axial control of ion motionincluding approaches for coupling to mass analyzers [Douglas et al, MassSpectrom Rev 24, 1, 2005].

The two main advantages of linear ion traps compared to the standard 3Dquadrupole ion trap include reduced space charge effects due to theincreased ion storage volume and enhanced sensitivity for externallyinjected ions due to higher trapping efficiencies [Schwartz et al, J AmSoc Mass Spectrom 13, 659, 2002]. Enhanced performance has beendemonstrated in a dual-pressure linear ion trap where ion selection andfragmentation process are optimized independently [Second et al, AnalChem 81, 7757 2009]. More complex arrangements involve mass selectiveaxial ejection techniques either based on fringe fields to convertradial ion excitation to axial motion [Londry & Hager, J Am Soc MassSpectrom 14, 1130, 2003] or on the use of vane lenses inserted betweenRF pole-electrodes and supplied with axial AC excitation waveforms[Hashimoto et al, J Am Soc Mass Spectrom 17, 685, 2006]. Theactivation-dissociation methods available are limited to CollisionInduced Dissociation (CID) and Electron Transfer Dissociation (ETD) andso far no more than two activation methods can be performed in tandem inthe same linear ion trap. Therefore, the development of novel designscapable of supporting a wide range of efficient activation-dissociationtools and methods and the ability to perform these sequentially isessential, particularly for the analysis of highly complex biologicalsamples and proteins.

A concept design of a collision cell with multiple potential regions forstoring and processing ions is disclosed in U.S. Pat. No. 7,312,442 B2.Although the proposed ability to sequentially activate and dissociateions using different techniques is highly desirable, the method neitherinvolves injection of charged particle beams for dissociativeinteractions nor is concerned with adjusting the DC electrical potentialand consequently the potential energy of the ions between multiplelevels, which greatly facilitates control of the interaction energy tooptimize activation-dissociation processes. Furthermore, advancedcontrol of the DC electrical potential and also the ion potential energyare critical for efficient ion transfer between trapping regionsincluding receiving and releasing ions with precise kinetic energy toand from a linear ion trap respectively. These new aspects require novelDC switching technology and methods disclosed in the present invention.

Techniques to control the interaction energy between ions stored in iontraps and externally injected electrons are disclosed in U.S. Pat. No.7,755,034 B2. In order to control the energy of the interaction in alinear ion trap three-state digital waveforms are employed whereelectrons are injected during the intermediate voltage state. Inaddition to the constrains in the mass range of the ions storedsuccessfully in the ion trap imposed by three-state RF trapping, thevoltage amplitude accessible for the intermediate state is also severelylimited and so is the accessible energy range available duringinteraction. Another disadvantage of the method disclosed for operatinga linear ion trap is the narrow time window for interactions to occur,which is limited to less than 1/3 of the waveform period. The methoddisclosed in the present invention alleviates all these problems bydecoupling the properties of the RF trapping waveform from the electronsource potential by the superposition of DC field components to controlthe potential energy of the ions independently and to any desired level.The mass range remains unaffected over an unlimited energy range and thetime of interaction is maximized.

Overall, the need remains for an improved linear ion trap and methodsfor activating and dissociating ions sequentially in a single apparatususing different techniques and performed with high efficiency.

SUMMARY

A linear ion trap arrangement configured with multiple segments isdisclosed providing at least two trapping regions formed by thesuperposition of multiple DC electrical field components to the main RFelectrical field component. Preferably, a trapping region consists of atleast three segments comprising four pole-electrodes and forming aquadrupole configuration. A trapping region may also consist of segmentsand end-cap electrodes. Opposite phase RF waveforms are applied to pairsof pole-electrodes to create the RF electrical field componentdistributed across the entire trapping volume to confine ions radially.Multiple DC electrical field components are formed by applyingswitchable DC electrical potentials to pole-electrodes or independentRF-free electrodes inserted between pole-electrodes to create trappingregions to facilitate axial control and also to define the potentialenergy of ions stored therein. Trapping regions are formed by loweringthe DC electrical potential of one of the DC field components in atrapping region with respect to neighboring DC electrical fieldcomponents creating a potential well. The terms RF electrical field andRF field are used interchangeably. The terms DC electrical field and DCfield are also used interchangeably.

The linear ion trap of the present invention further requiresalterations or switching of DC electrical potentials applied to generatethe DC field components forming a trapping region between a first DCpotential level and at least a second DC potential level. Switching ofDC electrical potentials can also be performed between three or more DCpotential levels. Preferably, the alterations or switching of thedifferent DC electrical potentials of a trapping region is performedsimultaneously.

Switching of DC electrical potentials and corresponding DC fieldcomponents forming trapping regions can be exercised in the absence ofions. Switching of a DC field component between two levels is alsoexercised to release from or receive ions in a trapping region.Preferably, switching of a DC field component is exercised followingalterations of the DC components forming a trapping region.

A direct consequence of controlling the DC electrical potentials andcorresponding DC field components forming a trapping region is theconcurrent alteration or switching of the potential energy of the ionsstored therein. Therefore, the linear ion trap of the present inventionfurther requires an alteration of the ion potential energy between afirst potential energy level and at least a second potential energylevel by raising or lowering, lifting or dropping the magnitude of theDC electrical potentials applied to generate DC field components forminga trapping region and further processing ions in at least one of theenergy levels respectively.

Processing in a trapping region of the linear ion trap of the presentinvention includes activation of ions using externally injected reagentions or reagent ions co-trapped with precursor ions, interactions withelectrons, manipulation of the mass-to-charge ratio of ions preferablyby electron detachment, proton attachment or charge reduction processes,interactions between ions and neutral molecules in ground or excitedstate, interactions with photons, excitation of ion motion usingauxiliary AC waveforms or duty cycle variations of the RF trappingwaveform, ion isolation using AC waveforms or duty cycle control,collisional activation dissociation, ion accumulation and transfer.Processing may involve one or more of the above functions to beperformed simultaneously or sequentially.

It is desirable to control the energy of interaction between ionspopulating at least one trapping region of the linear ion trap andexternally injected charged particles, for example ions and/orelectrons. It is also desirable to inject charged particles in-throughthe trapping region to activate ions stored at a first potential energylevel and subsequently alter or adjust the potential energy of processedions to a second potential energy level to perform a second processingstep. The second potential energy level may also facilitate transfer ofions from the first trapping region to a second trapping region orejection toward a mass analyzer. The second processing step may alsoinvolve external injection of electrons and/or reagent ions foractivation and dissociation experiments. The processing step performedin the first potential energy level may differ from the processing stepperformed in the second potential energy level of the first trappingregion. Sequential processing steps in a trapping region can beperformed by injecting electrons, while differentactivation-dissociation mechanisms can be enabled by adjusting thepotential energy of the ions during sequential interactions at differentenergy levels. The potential energy of the ions can be adjusted tooptimize processing in each of the first and second levels respectively.Processing steps in multiple potential energy levels can be executedduring a processing cycle.

In one example, Electron Capture Dissociation (ECD) requires thepotential energy of the ions to be less than 10 eV relative to thepotential energy of the electron source whereas electron detachment toreduce mass-to-charge ratio forming multiply charged radical ionsrequires a potential energy in excess of 10 eV, preferably in excess of30 eV. Electron Induced Dissociation (EID) via electronic-to-vibrationalexcitation requires electrons with even higher kinetic energies to beinjected in the trapping region populated with ions and extending theinteraction period. Controlling the potential energy of the ions betweenmultiple energy levels allows for all these differentactivation-dissociation methods to be performed sequentially. Newdissociation pathways become accessible by combing these techniques in amanner disclosed in the present invention.

The linear ion trap of the present invention further requires theapplication of a RF trapping waveform producing a substantially constantfield during at least a portion of the waveform period to permitinjection of charged particles with precise kinetic energy into thetrapping region. Charged particles are electrons produced in an electronsource or reagent ions produced in an ionization source. Chargedparticles can be injected periodically or continuously. Periodicinjection of charged particles in the ion trap is controlled by adeflector synchronized with the trapping waveform.

In a preferred exemplary embodiment of the present invention, the linearion trap comprises at least two trapping regions for processing ions. Afirst processing step involves trapping in a first potential energylevel where ions are preferably but not exclusively activated ordissociated, subsequently lifting the potential energy of the ions inthe first trapping region from a first level to a second level.Switching the DC level of one of the DC field components forming thefirst trapping region is applied to transfer ions to the second trappingregion for additional processing at a new potential energy level oreject ions toward a mass analyzer or an ion mobility spectrometer. Thesecond potential energy level of the first trapping region is preferablyadjusted relative to the potential energy level of the second trappingregion to suppress collisional activation during transfer. It is alsodesirable to process ions in the first and second trapping regionsrespectively at different potential energy levels and apply differentprocessing steps. Lifting and dropping the potential energy of the ionsin each of the trapping regions is necessary to transfer ions back andforth between the two trapping regions. For example, a second processingstep can be performed at the second potential energy level of the firsttrapping region. Adjusting the potential energy of the ions stored inthe first trapping region to a third level and switching one of the DCfield components can be exercised to eject ions toward the secondtrapping region. Consecutive processing steps can be performed in thesecond trapping region at different potential energy levels. Productscan be transferred back to the first trapping region or ejected toward amass analyzer by controlling the level of DC electrical potentialsforming the second trapping region in a synchronous manner and switchingone of the DC field components for subsequent release of ions. At leastone of the DC field components is switched between at least threedifferent DC levels during a processing cycle.

The ability to alter or adjust the DC electrical potentials andcorresponding DC field components between different levels in order tocontrol the potential energy of the ions greatly facilitates multipleprocessing steps performed in different trapping regions of the linearion trap at energy levels tailored to optimize specific processes.Potential energy alterations are essential for the optimization ofactivation-dissociation experiments by controlling the energy ofinteractions with externally injected charged particles and fortransferring ions in neighboring trapping regions for further processingat different DC electrical potential levels. The enhanced functionalityof the linear ion trap of the present invention is afforded by fasttransitions of selected DC electrical potentials to control ionpotential energy. Furthermore, adjusting the potential energy level ofthe ions is a highly efficient method to decouple the ionization sourcepotential from the operation of the linear ion trap. Ejection of ionstowards a mass analyzer or an ion mobility spectrometer can also beoptimized independently.

The diversity of experiments enabled through advanced control ofmultiple DC electrical potentials to alter or adjust the potentialenergy of the ions in different trapping regions of the linear ion trapis practically unrestricted. For example, ions can be processed in afirst trapping region at a first potential energy level. Lifting thepotential energy and switching one of the DC field components of thefirst trapping region can be applied in a manner to accelerate ions tokinetic energies sufficient for collisional activation dissociation tooccur inside the linear ion trap. Ions can be transferred and stored ina second trapping region whilst the DC field component of the firsttrapping region is relaxed to the original level. Switching of one ofthe DC field components in the second trapping region is preferablyapplied to receive and store ions efficiently therein. Re-accelerationis accomplished by lifting the potential energy in the second trappingregion and switching the same DC field component to release ions backtoward the first region extending the activation period in order toenhance the efficiency of dissociation. Oscillation of ions betweentrapping regions can be exercised independently or in combination withadditional processing steps performed sequentially. It is desirable todecelerate energetic ions inside a uniform RF field and not by applyinga stopping potential to end-cap electrodes, which are unsuitable forreflecting ions due to the presence of fringe fields associated withsignificant losses of higher mass ions. In this lift-switch mode ofoperation of the present invention the energy imparted to the ions uponcollisions with background gas molecules can be varied considerablyenhancing the efficiency of dissociation, particularly for high massions which are difficult to analyze with conventional slow heating CIDmethods.

In yet another preferred exemplary embodiment of the present invention,the linear ion trap comprises at least three trapping regions forprocessing ions. Most preferably each of the trapping regions isdesigned to support unique and independent processing functionalities.The ability to lift, reduce and adjust the potential energy of the ionsthrough control of the DC electrical potentials and corresponding DCfield components distributed across the linear ion trap is essential tooptimize tandem activation-dissociation experiments and any otherprocessing steps performed sequentially or simultaneously. Switching DCelectrical potentials between at least three potential levels is alsorequired to facilitate receiving and ejecting or transferring of ionsbetween trapping regions.

The diversity of experiments accessible with at least three trappingregions establishes the linear ion trap of the present invention apowerful analytical tool. For example, AC auxiliary waveforms to isolateor excite to activate ions can be performed in a first trapping region,activation using externally injected charged particles can be exercisedin a second trapping region, whereas additional activation steps orstorage and accumulation of products species to enhance signal-to-noiseratio can be performed in a third trapping region. Differences inpressure demand imposed by all these different functions can besatisfied by fast gas pulses using pulse valve technology.

It is desirable to pulse gas to access elevated pressures over a shortperiod of time while minimizing the gas load to neighboring vacuumcompartments. Elevated gas pressures are necessary to enhance collisioninduced dissociation, cool ions via collisions during processing ortransfer between trapping regions. Pulse gas also allows for operatingthe linear ion trap during ion isolation at low pressure. Preferably,the duration of a gas pulse for optimizing injection and transfer isless than 20 ms and at any instant in time pressure is uniformthroughout the linear ion trap. The duration of a gas pulse foroptimizing CID can be arranged to extend over a longer period of time.More than one pulse valve can be connected to the linear ion trap fordelivering different gases. Most preferably, the linear ion trap isdifferentially pumped.

The DC electrical potential control and consequently the potentialenergy adjustment functionality of the present invention requireswitching at least one of the DC field components between threedifferent DC levels. Switching DC electrical potential or DC voltagesapplied to segments between three or more DC levels is necessary tofully exploit the advantages associated with ion potential energycontrol in a linear ion trap designed with at least two trappingregions, most preferably in a linear ion trap designed with at leastthree trapping regions. Switching between three or more levelsfacilitates the releasing or receiving ions from or in a trappingrespectively. Therefore, the linear ion trap of the present inventionfurther requires the use of multiple state high voltage switchingtechnology. In a preferred circuitry design high voltage MOSFETtransistors are connected in series to enable DC switching between atleast three levels of the DC electrical potential. In another preferredcircuitry design a series of analogue multiplexers are employed whereeach multiplexer provides multiple output levels of each of the DCelectrical potentials applied to generate the DC field componentsdistributed across the linear ion trap. Individual analogue multiplexersor transistors connected in series can either be connected to individualsegments to create DC field components for axial control of ion motion.Alternatively, RF-free electrodes immersed in the RF field can be biasedto create the trapping regions for axial confinement and to transferions across the linear ion trap.

It is the purpose of the present invention to provide a linear ion trapcapable of supporting at least two different activation-dissociationtechniques, preferably at least three different activation-dissociationtechniques performed sequentially and enabled through multipletransitions of the DC electrical potentials and corresponding DC fieldcomponents to allow high level control of ion potential energy. Thesetransitions are supported by advances in electronics circuitry design.

More specifically, there is provided a linear ion trap comprising atleast two discrete trapping regions for processing ions, a RF generatorfor producing at least two RF waveforms, each RF waveform is applied toa pair of pole electrodes of said linear ion trap forming a RF trappingfield component to trap ions radially, a multi-output DC voltagegenerator for producing DC electrical potentials to generate DC fieldcomponents superimposed to the RF field component and distributed acrossthe length of the linear ion trap to control ions axially and a controlunit for switching each of the DC electrical potentials forming a firsttrapping region of said at least two trapping regions from a first levelto a second level respectively. Switching DC electrical potentials of atrapping region between a first and a second level is exercised to alteror adjust the potential energy of the ions stored therein between afirst and a second level respectively. Processing ions in at least oneof the potential energy levels in a first trapping region is performed.

The multi-output DC voltage generator generates multiple DC electricalpotentials applied to the linear ion trap and at least three DCelectrical potentials are applied to create DC field componentscollectively forming a single trapping region where at least one of theDC electrical potentials is switched between three different DC levels.Switching is exercised to transfer ions from a first to a secondtrapping region to perform a second processing step. Switching is alsoexercised to alter the potential energy level of the ions stored in asecond trapping region from a first to a second potential energy level.Processing ions in at least one of the potential energy levels in asecond trapping region is performed. Switching one of the DC electricalpotentials in a second trapping region between three different DC levelsis exercised.

Ions can be released from a first toward a second trapping region withsufficient kinetic energy to perform collision induced dissociation.Trapping in the second trapping region is preferably exercised prior toreleasing ions back to the first trapping region to extend the period oftime where ions undergo energetic collisions with background gasmolecules.

The linear ion trap further comprises a RF generator to generatewaveforms comprising of substantially rectangular or trapezoidal voltagepulse trains to create RF trapping field components which remainsubstantially constant during a significant portion of the waveformperiod. The linear ion trap also comprises a source of charged particlesand optics to form a beam of charged particles injected through a firsttrapping region containing ions at a first potential energy level, at asecond potential energy level or at multiple potential energy levels.

The linear ion trap is configured to receive and thermalize ions from anionization source at a first potential energy level, to processes ionsat a second and a third potential energy level, and finally to ejections thermalized at a fourth potential energy level toward a massanalyzer or an ejector coupled to a mass analyzer for measuringmass-to-charge ratios. Direct ejection from a trapping region of thelinear ion trap to a mass analyzer is also envisaged.

A linear ion trap is provided comprising at least two discrete trappingregions for processing ions, a RF electrical potential generator forproducing two RF waveforms, each applied to a pair of pole electrodes ofthe linear ion trap forming a RF trapping field component to trap ionsradially, a multi-output DC electrical potential generator for producingmultiple DC field components superimposed to the RF field component anddistributed across the length of the linear ion trap to control ionsaxially, and a control unit configured to switch the DC electricalpotentials and corresponding DC field components collectively forming afirst trapping region populated with ions to alter ion potential energyfrom a first level to a second level, and to perform a first ionprocessing step in at least one of the levels.

The control unit is configured to switch at least one DC field componentof DC field components collectively forming a first trapping regionbetween three different DC electrical potential levels. The control unitis configured to switch at least one DC field component to transfer ionsfrom a first trapping region to a second trapping region to perform asecond processing step. The control unit is configured to switch the DCfield components collectively forming a second trapping region to alterthe potential energy of ions stored therein from a first level to asecond level. The control unit is configured to switch at least one DCfield component of DC field components collectively forming a secondtrapping region between three different DC electrical potential levels.

The RF waveforms comprise substantially rectangular voltage pulsetrains. A pair of pole electrodes is configured to receive a beam ofcharged particles injected through a first trapping region populatedwith ions at a first potential energy level.

The control unit is configured to switch multiple DC field components torelease ions from a first trapping region toward a second trappingregion with sufficient kinetic energy to perform collision induceddissociation. The control unit is configured to switch at least one DCfield component to eject processed ions toward a mass analyzer formeasuring mass-to-charge ratio.

Methods for processing ions in a linear ion trap are also disclosed. Inone exemplary embodiment, the method comprises providing a linear iontrap defining a trapping field with a substantially uniform pressure ata given instant in time, trapping ions in the trapping field produced bythe superposition of a RF trapping field component for radialconfinement of the ions and multiple DC field components for axialcontrol of the ions, distributing the DC field components along the axisof the linear ion trap to form at least two discrete trapping regions,subjecting ions in a first trapping region at a first potential energylevel to a first processing step, and switching the DC field componentscollectively forming the first discrete trapping region in a timelymanner to alter the potential energy of the ions from a first level to asecond level.

The method further comprises switching at least one DC field componentof a first trapping region between three different levels to facilitateion transfer to a second trapping region. The method further comprisesaltering the potential energy of the ions in the second trapping regionfrom a first potential energy level to a second potential energy leveland processing ions in at least one of the levels. The method furthercomprises subjecting ions to a second processing step in the secondpotential energy level of the first discrete trapping region. The methodfurther comprises subjecting ions to third processing step in a first ora second potential energy level of the second discrete trapping region.The method further comprises producing the RF trapping field componentby two opposite phase RF waveforms comprising substantially rectangularvoltage pulse trains. The method further comprises injecting a beam ofcharged particles through the trapping region to activate ions in atleast one of the first, second and third processing steps.

In another exemplary embodiment, a method for processing ions in alinear ion trap comprises providing a linear ion trap defining atrapping field at a substantially uniform pressure at a given instant intime, trapping ions in the trapping field produced by the superpositionof a RF trapping field component for radial ion confinement and multipleDC field components for axial control of the ions, distributing the DCfield components spatially to form at least two discrete trappingregions along the axis of the linear ion trap, subjecting ions in afirst trapping region at a first potential energy level to a firstprocessing step, subjecting ions in a second trapping region at a secondpotential energy level to a second processing step, transferringprocessed ions between trapping regions by switching DC field componentscollectively forming trapping regions to alter the potential energy ofthe ions stored therein, and switching at least one DC field componentbetween three different DC electrical potential levels.

In yet another exemplary embodiment, a method for processing ions in alinear ion trap comprises providing a linear ion trap defining atrapping field with a substantially uniform pressure at a given instantin time, trapping ions in the trapping field produced by thesuperposition of a RF trapping field component for radial ionconfinement and multiple DC field components for axial control of theions, distributing the DC field components spatially to form at leastthree discrete trapping regions in said linear ion trap, subjecting ionsin the first trapping region at a first potential energy level to afirst processing step, subjecting ions in the second trapping region ata second potential energy level to a second processing step, subjectingions in the third trapping region at a third potential energy level to athird processing step, transferring processed ions between trappingregions by switching DC field components collectively forming trappingregions to alter the potential energy of the ions stored therein, andswitching at least one DC field component between three different DCelectrical potential levels.

A method for processing ions in a linear ion trap according to anotherexemplary embodiment comprises a linear ion trap defining a trappingfield produced by the superposition of a RF trapping field component forradial ion confinement and multiple DC field components for axialcontrol of the ions, distributing the DC field components spatially toform at least two discrete trapping regions along the axis of the linearion trap, subjecting ions in the first trapping region at a firstpotential energy level to a first processing step, altering thepotential energy of the ions, and switching at least one DC fieldcomponent between three different DC electrical potential levels torelease ions from the first trapping region.

In another exemplary embodiment, the present invention also provides amethod of moving ions along the axis of a linear ion trap. The methodcomprises generating a RF electrical potential for confining ionsradially relative to the axis within a trapping region of the ion trap,generating multiple DC electrical potentials defining a trapping regionfor axially confining ions within the trapping region whereby the RF andDC electrical potentials collectively trap ions within the trappingregion, simultaneously changing the DC electrical potentials of thefirst trapping region between a first level and a second level, andchanging DC electrical potentials at the second level at one side of thetrapping region to a value not exceeding the minimum DC electricalpotential of the trapping region thereby permitting the release of ionsconfined therein for movement along the axis.

In the foregoing exemplary embodiment, the ion trap may comprises aplurality of segments arranged sequentially in an array extendingparallel to the axis for generating and shaping the spatial profile ofthe DC electrical field. The method further includes providing a finitenumber of different substantially constant DC voltages for generatingeach DC electrical field and applying a respective one of the DCelectrical voltages to a respective one of a plurality of segments ofthe ion trap.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a schematic diagram of the linear ion trap system includingthe RF and DC generators and a control unit to control RF and DCelectrical potentials and ion potential energy.

FIG. 1B is a perspective view of a segmented linear ion trap configuredwith a single trapping region and associated transitions of the DCelectrical potential to control ion potential energy.

FIG. 2 is a perspective view of a segmented linear ion trap configuredwith two trapping regions and associated transitions of the DCelectrical potential to control ion potential energy.

FIG. 3A is a circuitry diagram of switching electronics to control DCfield components between multiple levels.

FIG. 3B is a circuitry diagram of switching electronics to control DCfield components between multiple levels.

FIG. 3C is a circuitry diagram of switching electronics to control DCfield components between multiple levels.

FIG. 4 is a schematic diagram of a mass spectrometer configured with asegmented linear ion trap including the transitions of the DC electricalpotential profile to control ion potential energy.

FIG. 5 is a schematic diagram of a mass spectrometer configured with asegmented linear ion trap including the transitions of the DC electricalpotential profile to control ion potential energy.

FIG. 6 is a schematic diagram of a mass spectrometer configured with asegmented linear ion trap including the transitions of the DC electricalpotential profile to control ion potential energy.

FIG. 7 shows the transitions of the DC electrical potential profile tocontrol ion potential energy for the mass spectrometer shown in FIG. 6.

FIG. 8 shows the transitions of the DC electrical potential profile tocontrol ion potential energy for the mass spectrometer shown in FIG. 6.

DETAILED DESCRIPTION

A general description of a linear quadrupole ion trap of the presentinvention is provided with reference to FIG. 1A. The linear ion trap 100is connected to a RF generator 102 producing two RF waveforms, eachapplied to a pair of pole electrodes of the linear ion trap forming a RFtrapping field component to trap ions radially. The linear ion trap 100is also connected to a multi-output DC generator 103 producing multipleDC electrical potentials forming multiple DC field components 105superimposed onto the RF field component and distributed across thelength of the ion trap to control ions axially. A control unit 104(e.g., FPGA control unit 346 further described below with reference toFIG. 3C) is used to define the characteristics of the RF waveforms andalso the timing and the switching of the DC electrical potentialsbetween different levels. The linear ion trap is preferably configuredwith two discrete trapping regions 101 for processing ions therein. Thelevels of the DC field components forming a discrete trapping region arearranged to form a potential well 106 to confine ions axially and thecontrol unit is configured to collectively adjust or alter the level ofthe potential well in a timely manner. The control unit 104 is alsoconfigured to switch a DC field component between three different levels107.

A description of a linear quadrupole ion trap is provided with referenceto FIG. 1B. The linear quadrupole ion trap 110 comprises three segments111, 112 and 113 where each segment is formed by two pairs ofpole-electrodes and each pair is supplied with opposite phase RFwaveforms to form the RF field component for trapping ions radially. Allsegments share a common axis 114 and collectively define a trappingregion for processing ions. Independent DC electrical potentials areapplied to segments forming three DC field components respectively foraxial control of the ions. The magnitude of the DC field componentapplied to the central segment 112 is lower relative to the neighboringDC field components to form a potential well and confine ions axially.The central segment is also designed with inlet apertures 115 on thepole-electrodes to accept charged particles generated externally in acharged particle source 116. Injection of charged particles through theapertures 115 on the poles is facilitated by a focusing lens system 117.

The transitions of the DC electrical potential or the potential energysurface along the axis of the linear ion trap of the present inventionare also shown at 118. Ions are processed and/or activated by injectingcharged particles with the desired kinetic energy determined by the DCelectrical potential level of the charged particle source 120 relativeto the first DC electrical potential level 119. The potential energy ofthe ions is subsequently raised 121 to a second energy level 122 where asecond activation processing step can be performed. In this basicconfiguration switching 123 of the DC field component applied to segment113 between three different DC levels or DC electrical potentials 124,125 and 126 is necessary to facilitate ion transfer or ejection. Thefirst DC electrical potential 126 is adjusted to a level higher than thepotential applied to the central segment 122 to confine ions axially,the second potential 124 is a result of alterations of the of the levelof the potential well 121 to facilitate ion processing at a second DCpotential level 122 while the third DC potential level 125 is applied torelease ions from the central segment 112. Switching DC electricalpotentials between three different levels is necessary to control thekinetic energy of the ions, for example matching the acceptance energyof a mass analyzer during ejection of ions stored in the potential wellor controlling the energy in binary collisions with buffer gas moleculesduring transfer.

The DC electrical potential control functionality 121 greatlyfacilitates multiple processing steps to be realized by adjusting thepotential energy of the ions to optimum levels for injection of chargedparticles with different kinetic energies. In eachactivation-dissociation step the energy of the interaction is determinedby the relative DC potential level the ions stored at in the centralsegment 112 and the DC potential level of the charged particle source116. For example, electron capture dissociation, electron induceddissociation and electron detachment for charge state manipulation canall be performed in the same trapping region by simple adjustments ofthe DC electrical potential ions are stored at in the trap between threedifferent levels.

A description of a preferred exemplary embodiment of the presentinvention is provided with reference to FIG. 2. The linear quadrupoleion trap 200 consists of two trapping regions formed in segments 202 and207, entrance-end and exit-end guard segments 201 and 208 respectivelyand intermediate guard segments 203-206 having a common axis 209 andcollectively defining a trapping volume for processing ions. Thetrapping region formed in segment 202 is designed with inlet apertures210 on a pair of pole-electrodes. A charged particle source 211 forinjecting charged particles through a focusing lens 212 is connectedexternally to the linear ion trap 200. The second trapping region insegment 207 is preferably supplied with AC auxiliary waveforms toperform ion isolation and excitation of ion motion for collisionalactivation or dissociation.

The transitions of the potential energy surface of the segmented linearion trap 200 are also shown 213. A processing cycle may includetransferring ions into the linear ion trap in the first trapping regionin segment 202 at a first DC electrical potential level 214. Ionsintroduced into the linear ion trap can be pre-selected using aquadrupole mass filter. Ion processing including activation anddissociation using externally injected charged particles generated inthe particle source 211 is performed at a first potential level 214 orany other level necessary to optimize the efficiency of the process.Subsequently, the DC potential applied to the guard segment 203 isswitched 217 between levels 215 and 216 to transfer ions to the secondtrapping region in segment 207 for subsequent processing at a differentDC potential level 219.

A weak DC gradient 218 can be established between trapping regions tominimize energetic collisions with background gas molecules. Iontransfer can be performed at constant background pressure or during agas pulse. Fast ion thermalization via collisions is achieved during agas pulse or at constant elevated pressure. In contrast, ionthermalization at lower pressure is accomplished over an extended periodin time where ions oscillate between trapping regions. Switching the DCpotential 220 applied to the exit-end guard electrode 208 to a higherlevel is required to prevent ions from leaking out through the secondtrapping region of the ion trap 200.

Processing in the second trapping region in segment 207 may involve anyof the processing steps performed using AC auxiliary waveforms, forexample ion isolation or excitation of ion motion for collisionalactivation. The potential energy of ions selected using AC auxiliarywaveforms or product ions generated in segments 207 or 202 can be raised221 to a new level 222 for subsequent release toward a mass analyzer.The ejection process requires additional switching 223 of the DCelectrical potential applied to segment 208 between levels 224 and 225.Alternatively, the potential energy of selected or product ions israised to a higher level 226 for efficient transfer back to the firsttrapping region in segment 202. Transfer requires additional switching227 of the DC potential applied to segment 206 between levels 228 and229. Similarly, a weak DC gradient 230 is preferably established duringtransfer of ions between segments 207 and 202. Ions are trapped andfurther processed at the new DC electrical potential level 231.Processing can also be performed at a different level by switching 232the DC field components in the first trapping region to a new level.Relaxing or raising the potential energy of the ions to the originallevel 214 in the first trapping region is necessary to optimize iontransfer to the second trapping region. The processing cycle describedhere can be repeated using the same or new processing steps.

The significant advantage of the ion potential energy controlfunctionality enabled by DC switching of electrical field componentsbetween multiple levels during a single experimental cycle describedwith reference to FIG. 2 allows for elaborate multiple-stage or tandemin space and in time activation dissociation experiments to be performedefficiently. More importantly, the ion potential energy controlfunctionality offers the unique advantage to select different activationdissociation tools and methods to be applied in each step of anexperimental cycle without imposing restrictions in the energy ofinteraction between charged particles and ions or any other restrictionswith regard to the energy acceptance requirements imposed by neighboringion optical elements including ejection to a mass analyzer and an ionmobility spectrometer.

With reference to FIG. 2, multiple processing steps can be performed inthe first trapping region simultaneously or sequentially, at the same orat different DC electrical potential levels using a single or differentcharged particle beams operated in a pulsed or in a continuous manner.Pulsed injection of charged particles in a trapping region requiresgating to be applied. Gating is preferably synchronized with the phaseof the trapping waveform. Two processing steps can be exercised in asingle trapping region simultaneously, for example the application of ACauxiliary waveforms for excitation of ion motion and injection ofelectrons for ion activation and dissociation. Excitation of ion motionof selected ions during electron irradiation can be used to control thekinetics of activation or to minimize charge reduction andneutralization of ions. Additional charged particle sources can becoupled to different trapping regions of the linear ion trap. Processingin different trapping regions can be performed simultaneously orsequentially using the same or different group of ions.

In the example disclosed with reference to FIG. 2, the DC electricalpotentials forming the DC field components are applied directly to thesegments through resistors and capacitors. It is also desirable to DCbias independent electrodes inserted between RF pole-electrodes tosuperimpose the DC field components to the RF field component across thelinear ion trap.

Circuitry diagrams of the present invention to enable multiple stateswitching of DC electrical potentials and facilitate the ion potentialenergy control functionality are presented in FIG. 3A, 3B and 3C. FIG.3A shows a circuitry diagram of the switching design 300 of theinvention. In this example only two segments 303 and 304 of the linearion trap are shown for simplicity and connected to a switching card 302,which is floated onto a second lift card 301. The lift card is designedto switch DC potentials or DC voltages applied to the segments betweentwo different levels determined by the voltage output of two independentpower supply units V1 and V2 respectively. The lift voltage isdetermined by switches SW1 and SW2 and the voltage output of the powersupplies. The output of the lift card is connected to a third powersupply unit V3 and an additional set of switches SW3A and SW3B in seriesand finally connected to the first segment 303. Similarly a fourth powersupply unit V4 and switches SW4A and SW4B are also connected in serieswith the lift card and determine the voltage applied to the secondsegment 304. Table 305 summarizes the possible DC electrical potentialsor DC voltage output levels that can be applied to each of the first andsecond segments respectively.

The float card 302 can accommodate additional pairs of switches andpower supply units to connect to additional segments or independent DCelectrodes of the linear ion trap. The float cards can be connected inseries to the same or different lift cards. Grouping of specific floatcards in series with two or more lift cards connected to individualsegments maybe desirable to facilitate fast and independent switching ofthe DC field components in each of the trapping regions establishedacross the linear ion trap. The polarity of the power supply units inboth lift and float cards can be varied accordingly.

FIG. 3B shows another possible arrangement of four switches and thecorresponding power supply units that can be employed for fast switchingthe voltage applied to a single segment between four different levels.This switching configuration can be floated on an independent lift card.

Processing cycles where more than three DC electrical potentials, DCvoltages or levels of the DC field components are necessary tofacilitate multiple-stage sequential activation dissociation, achieveefficient ion transfer between trapping regions, as well as receive ionsand transfer products to the mass analyzer with the appropriate kineticenergy. More importantly, multiple DC state switching enables precisecontrol of the potential energy of the ions through adjustments of theDC electrical potentials and corresponding DC field components acrosssegments in a synchronous manner.

FIG. 3C shows a preferred electronics circuitry diagram 340 designed toapply eight different DC voltage levels to a single segment of the LQITduring the course of a processing cycle. The board 341 is populated witha DAC 342 driving an analogue multiplexer (MUX) 343 with eight output DCstates connected to an operational amplifier 344, which in turn isconnected through leads and vacuum feedthroughs 345 to a single segment.Both positive and negative potentials can be generated, typicallylimited to ±225V by the model of the operational amplifier. The numberof DC states is typically controlled through a PC unit 347 which isconnected to the FPGA (Field-Programmable Gate Array) control unit 346.The FPGA control unit 346 provides the control signals to themultiplexer and also forwards information to the microcontroller unit348 for the DAC to generate the appropriate DC voltage levels. A secondboard identical to board 341 connected to the same MCU 348 andcontrolled in a synchronous manner through the FPGA control unit 346 isrequired for driving a second segment. Combinations of multiplexers andbidirectional switches are also advantageous for facilitating complexswitching and advanced ion potential energy control. The FPGA controlunit is further configured to control the characteristics of thesubstantially rectangular opposite phase RF waveforms including the RFamplitude, frequency and duty cycle. The FPGA control unit is alsoconfigured to control the properties of the auxiliary AC waveformspreferably applied in dipolar mode.

An exemplary embodiment of the present invention is described withreference to FIG. 4. The schematic diagram of the instrument 400 shows asegmented Linear Quadrupole Ion Trap (LQIT) attached to an atmosphericpressure interface where ions are transferred by intermediate pressure,gas dynamically optimized ion optics, through a RF ion guide into asubsequent vacuum region incorporating a preferred embodiment of thepresent invention. Ion mass-to-charge is measured using an oTOF massanalyzer.

Ions are generated by electrospray ionization 401 and sampled through acapillary inlet 402 into a first vacuum compartment 403 accommodatingthe aerolens 404. The function and properties of the aerolens aredescribed in WO2014001827 and EP 2864998A2, the disclosures of which areincorporated herein by reference in their entirety. In brief, thesupersonic jet 405 discharges into the bore of the aerolens, which isdimensioned to restrain radial expansion of the gas to form a laminarsubsonic gas flow entraining charged clusters and ions. Pressure in thefirst vacuum compartment 403 is maintained at >1 mbar, preferably >10mbar pressure using a mechanical pump 406 to enlarge the inlet systemand enhance sampling efficiency from the ionization source. Ions aredirected through a lens system 407 into a RF octapole 408 described inU.S. Pat. No. 9,123,517(B2), the disclosure of which is incorporatedherein in its entirety. The RF octapole combines an octapolar fielddistribution 409 to capture ions at the entrance of the ion guide and aquadrupolar field distribution 410 to compress ions radially andmaximize transmission through the differential aperture 411. Aturbomolecular pump 412 is connected to a vacuum compartment 413accommodating the RF octapole 408 to achieve a pressure in the range of10⁻³- 10⁻² mbar. Ions are kinetically thermalized in the RF octapole andtransmitted through differential apertures 411 into the linear ion trap414 of the present invention for processing. After processing ions arereleased from the LQIT through a RF hexapole ion guide 431 disposed in asubsequent vacuum compartment 433 evacuated by a turbomolecular pump 432toward an orthogonal TOF mass analyzer 437 operated at high vacuumcontrolled by a turbomolecular pump 438. In this preferred configurationions are transferred from the hexapole 431 through a set of differentialapertures 433 into a high vacuum lens 434, a slicer 435 and finallyundergo orthogonal acceleration by the application of high voltageextraction pulses to the electrodes of the orthogonal gate 436.

In the embodiment shown in FIG. 4. the LQIT is constructed withhyperbolic pole-electrodes 415. Substantially rectangular trappingwaveforms with 180° degree phase shift 416 are applied to oppositepole-electrodes. Rectangular or other types of trapping waveformsforming a substantially constant RF trapping field component during partof the waveform period are necessary for efficient interactions betweentrapped ions and externally generated ions and electrons. The LQIT ispreferably encapsulated into a differentially pumped region 428connected to a turbomolecular pump 427. Pulse valves to dynamicallycontrol pressure in the trapping region and leak valves to controlbackground pressure are connected to the LQIT. The LQIT is preferablydisposed in vacuum compartment 430 accommodating the RF hexapole 431 andoperated at lower pressure. Scattering of ions during ejection from theLQIT is therefore minimized and so is the axial kinetic energy spread.

The LQIT is designed with nine segments 417-425 where each segment issupplied with a switchable DC electrical potential to form trappingregions in segments 418, 421 and 425. Processing in the first trappingregion in segment 418 involves ion collection and storage, ionaccumulation, excitation of ion motion for isolation of a singlemass-to-charge ratio or multiple precursor ions, slow heating collisioninduced dissociation using dipolar excitation, broadband excitation orDC dipolar excitation methods, activation without driving ions todissociation and combinations thereof. The third trapping region insegment 425 is designed for storing and accumulating product ions priorto ejection toward the oTOF pulser 436 with the appropriate energy,satisfying the demand imposed by downstream optics and the massanalyzer. In a simple mode of operation raising the potential energy ofthe ions stored in segment 421 above the potential applied to segment425 and subsequently switching appropriate DC field components isexercised to transfer ions efficiently between trapping regions.

Enhanced CID efficiency is obtained by superimposing auxiliary ACwaveforms, preferably but not exclusively applied in dipolar mode, tothe RF electrical field produced by substantially rectangular RFwaveforms confining ions radially and by adjusting the duty cycle tovalues other than 0.5. Variations in the duty cycle are used to generateasymmetric and substantially rectangular waveforms to fine control theproperties ion motion within the ion trap by creating an asymmetric ionmotion. Most preferably, the direction of the asymmetric ion motionproduced by varying the duty cycle of the RF waveforms is alignedrelative to the direction of dipolar excitation to maximize the kineticenergy of ion vibrations in the ion trap without causing unwantedejection. The energy deposited to the ions in the presence of a buffergas under such trapping conditions is enhanced and so is fragmentationefficiency.

In another preferred configuration a first symmetric RF waveform isapplied to the first pair of pole-electrodes and a second asymmetricwaveform is applied to the second pair of pole-electrodes and furthercombined with an AC auxiliary waveform to excite ion motion to enhancethe efficiency of CID. Applying a first symmetric RF waveform and asecond opposite phase asymmetric RF waveform to the first and secondpairs of pole-electrodes of a given segment of the ion trap respectivelycreates a second fundamental secular frequency of the ion motion andpermits higher amplitude excitation waveforms to be applied withoutcausing unwanted ejection. The duty cycle offset between the RFwaveforms, excitation frequency and amplitude and also the q parameterof the ions on the stability diagram can be tuned to enhance theefficiency of CID.

Activation using electrons and reagent ions injected into the LQIT isperformed in the second trapping region in segment 421. Examples of ionactivation using externally generated charged particle beams includeECD, EID, electron detachment to reduce m/z ratio of precursor speciesproducing multiply charged radical ions and other types of ion-electroninteractions. External injection of reagent ions for ion-ion collisionalactivation and ion-ion reactions is also allowed. Ion-molecule reactionsto form adduct species and fragments in addition to photo-fragmentationexperiments can also be performed in segment 421.

In the case where interactions between trapped ions and electrons areconsidered, it is desirable to adjust first the DC field componentsforming the second trapping region to levels sufficiently lower comparedto the potential energy level electrons are generated at to establishenergetic interactions sufficient to detach electrons, create multiplycharged radical species and reduce the m/z ratio of precursor ions.Efficient production of multiply charged radical ions is desirable toenhance activation dissociation experiments performed in subsequentprocessing steps. For example, subjecting multiply charged radical ionsto CID and ECD experiments is expected to open up new dissociationpathways and enhance the analytical information currently available withexisting activation-dissociation tools and methods. Controlling thepotential energy of the ions during the course of an experiment is themost critical aspect enabling different activation tools to be employedsequentially.

It is also suitable to perform EID experiments by extending irradiationperiod of precursor ions with energetic electrons.Electronic-to-vibrational energy transfer is an alternative method toproduce CID type ions and obtain enhanced sequence coverage. It is alsopossible to perform charge reduction experiments by irradiating multiplycharged precursor ions with slow electrons. These functions andassociated dissociation pathways become easily accessible by adjustingthe potential energy level of the ions through alterations of the DCelectrical potentials and corresponding DC field components superimposedonto the RF trapping field forming trapping regions for processing ions.

Producing multiply charged radical ions from precursor ions usingenergetic electrons or performing charge state reduction experiments areboth efficient in controlling the charge state distribution of the ions.In this type of experiments frequency jumps of the RF trapping waveformare required to perform subsequent activation steps. For exampleelectrons can be injected in the second trapping region at a first DCelectrical potential level to generate multiply charged radical ionswith reduced m/z ratios. The potential energy of product ions can thenbe lowered to levels sufficient for ECD to be performed. The m/z ratioof the multiply charged radical species produced in a first processingstep and subsequently subjected to ECD can be matched to the m/z ratioof the ECD products to cover the widest range of m/z ratios storedsuccessfully in the trap. This method enhances the analyticalinformation that can be extracted during the course of a singleexperiment.

In another mode of operation of the present invention shown in FIG. 4,reagent ions generated in a discharge ionization source or by means ofElectrospray Ionization (ESI) or other ESI variants known to thoseskilled in the art are introduced into the LQIT for ion-ion activationand ion-ion reaction experiments. Similarly, it is desirable to controlthe energy of the interaction between reagent and precursor ions, mostpreferably scan the energy of interaction by adjusting the potentialenergy of the ions in segment 421 to optimize product ion formation.Adjusting the DC field components in the second trapping region toidentify optimum conditions for activation-dissociation studies is amore straight forward approach than adjusting the potentials appliedalong the entire reagent ion optical line.

The application of trapping waveforms, which exhibit a constant RFtrapping field component over part of the waveform period greatlyfacilitates external injection of ions and electrons into the LQIT.Reagent ions and electrons can be injected in the trapping region withprecise kinetic energy to optimize activation and dissociationexperiments. It is the scope of the present invention to tune the energyof activation and dissociation by adjusting the potential energy of theions stored in the second trapping region in segment 421 over a verywide range or between different levels. It is also the scope of thepresent invention to provide new tools and methods to perform ionactivation experiments simultaneously and sequentially to enhance theanalytical information extracted during the course of a multiple-stageactivation-dissociation experiment. Most importantly, the differentactivation techniques, which involve interactions with externallyinjected charged beams, can be optimized independently and newdissociation pathways become available through alterations of thepotential energy of the ions.

It is also desirable to perform different activation processessimultaneously for example irradiating ions with photons and electrons,or photons in the presence of reagent molecules. Reagent molecules arepreferably introduced into the LQIT using a pulse valve and exhibit aresidence time of the order of 10-100 ms.

In another preferred mode of operation, ions are stored using atwo-state substantially rectangular trapping waveform and irradiated byreagent ions or electrons during a first half of the waveform period andwith electrons during the second half to generate two different types offragment ions simultaneously. The potential energy of the ions andproducts can be maintained constant or switched from a first level to asecond level to adjust the energy of ion-ion and ion-electroninteractions independently.

Interactions between ions stored in the LQIT in the second trappingregion in segment 421 and externally generated charged particles andphotons is facilitated by apertures on two opposite pole-electrodes insegment 421. Preferably, during the course of an experiment electron orreagent ion source optics are operated at fixed potentials and optimizedfor maximum transmission through the lens system 426 and through theexit aperture on the opposite pole-electrode to minimize surfacecontamination and charging. Focusing of ions and electrons through theapertures is accomplished in part by appropriate selection of voltagesapplied to the focusing lenses 426.

Different activation-dissociation procedures, especially those utilizingexternally injected charged particle beams and in combination withstandard fragmentation techniques become apparent only after realizingthe possibility to switch and control the DC electrical potentials andas a result the potential energy of the ions between different levels indifferent trapping regions of the LQIT in order to fine tune interactionenergies and also transfer ions efficiently. All the new methods arefacilitated by advances in electronics as disclosed in the presentinvention in FIGS. 3A, 3B and 3C.

An example of a switching sequence of the DC profile 439 across the LQITwhere at least one segment is switched between three different DC levelsduring the course of an experiment is presented in FIG. 4. Ions aretransferred and accumulated in the first trapping region by lowering theDC electrical potential 440 in segment 418 relative to the DC potentialsapplied to neighboring segments. Ions are mass selected using ACauxiliary waveforms applied in dipolar mode to a single pair ofpole-electrodes. After the completion of the first processing stepprecursor ions are transferred to the second trapping region in segment421 by switching the DC field components 441 across the first threesegments of the LQIT, 417, 418 and 419. Ions stored in the potentialwell 442 are subjected to a second processing step using externalinjection of energetic electrons to form multiply charged radical ions.This is accomplished by lifting the potential energy of ions 443 whilethe electron source is maintained at ground potential. A thirdprocessing step is performed by dropping the potential energy 443 ofproduct ions to levels appropriate for ECD. In this example electrondetachment to form multiply charged radical ions is performed with ˜45eV electrons and ECD with ˜1 eV electrons. Finally, lifting the ions tothe same energy level and switching DC potentials applied to segments422-425 is applied to transfer ions 444 to the end segment 425 tooptimize ejection 445 toward the oTOF mass analyzer.

Different experiments based on the same switching sequence can beperformed, for example ions can be received in the potential well 440and subjected to ECD without prior irradiation with energetic electrons.A deflector is synchronized with the transitions of the DC profile toprevent electrons from entering the trap when the potential energy ofthe ions stored in segment 421 is not appropriate for ECD to take place.Subsequently, ECD products ions can be transferred to segment 418 forisolation-selection of new precursor species and slow heating CIDenabled by advanced control of DC electrical potentials and theswitching methodology disclosed in the present invention.

Control of the DC electrical potential in populated trapping regionsdecouples the energy imparted to the ions during interactions withexternally generated electrons and the requirements imposed for iontransfer and ejection from the trap. Potentials applied to segments canbe freely adjusted to any level or multiple levels during a singleexperiment and this is made possible by advancements in electronics andthe circuitry disclosed in the present invention.

Another exemplary embodiment of the present invention is shown in FIG.5. The schematic diagram of the instrument 500 shows the segmented LQIT501 attached to a mass spectrometric platform 502 which incorporates anorbitrap mass analyzer 510. Typically ions are mass selected in aQuadrupole Mass Filter (QMF) 503 and pass through differential apertures504, 506 and a hexapole ion guide 505 to an ejection trap 507. Ions aresubsequently injected through a deflector lens 509 into the orbitrap 510for mass analysis or transferred axially to a RF hexapole 511 forcollisional activation-dissociation. Ions can be transferred to thesegmented LQIT 501 for a more comprehensive activation-dissociationanalysis by lowering potentials applied to the differential aperturelenses 512. The LQIT is preferably differentially pumped and gas canescape only through apertures on pole electrodes and two end-electrodesdisposed on either end of the LQIT, 512 and 522. The LQIT can beentirely immersed into a separate external vacuum compartment evacuatedby a second turbo pump. Pulse valves, leak valve and a pressure gaugeare preferably connected to the LQIT to control and monitor pressure.

The segmented LQIT in this exemplary embodiment is designed with ninesegments in total 513-521 and three trapping regions formed in segments,514, 517 and 520. The length of each of the active segments is optimizedto perform specific functions with high efficiency. The first trappingregion centered on segment 514 is extended in length to accommodate alarger number of charges and minimize space charge effects and relatedfrequency shifts in order to perform resonance excitation for isolationof single or multiple precursor ions with high efficiency. Segment 514is also designed to perform slow heating CID of single or multipleprecursor ions during pulse gas introduction or under static backgroundpressure. CID excitation can be performed with waveforms designed withsingle or multiple excitation frequencies. Other typical experimentswith FNF or SWIFT waveforms applied to segment 514 may include multipleprecursor selection, multiple precursor excitation and ion ejectionusing waveforms designed with single or multiple notches across thesecular frequency range of stored ions.

The second trapping region in segment 517 is designed with entranceapertures on at least two of the pole-electrodes to allow for externallygenerated ions, electrons, photons and radicals to be injected and reactwith ions preselected in segment 514, or using the QMF 503. Preferably,the trapping waveform is substantially square to generate a constanttrapping field during half of the waveform period to inject ions orelectrons with precise kinetic energy. Other trapping waveforms designedwith three voltage states can be employed to facilitate externalinjection of charged species with variable energies. Positive andnegative ions or electrons can be injected simultaneously, sequentiallyor independently through the entrance apertures to activate, ionize,react and dissociate selected ions. The length of segment 517 is reducedcompared to 514 to allow for greater axial compression to increasecharge density and maximize interaction with externally injectedspecies.

The third trapping region in segment 521 is designed to store andaccumulate product ions from consecutive processing steps performed inthe LQIT 501. Additional activation can be performed in this segmentusing photons directed perpendicular through the ion trap axis escapingthrough window ports attached to the vacuum compartment. Accumulatedions are then released from segment 521 back to the ejection trap 507for analysis using the orbitrap 510.

The switching sequence of the DC electrical potential profile during anexample of a processing cycle 523 is described in FIG. 5 where ions 527released from the ejection trap 507 or selected in the QMF 503 aretransferred through the hexapole ion guide 511 into the LQIT 501 andstored in segment 517. The DC potential across the ion trap 524 israised at the far end segments during injection into the LQIT tofacilitate efficient capturing of ions with elevated axial kineticenergy. The arrival time of the ions in the LQIT is preferablysynchronized with a gas pulse to kinetically thermalize ions 528 insegment 517 during the pressure transient. DC potentials aresubsequently switched 525 to raise the potential energy of the ions 528to adjust the kinetic energy of interaction with externally injectedions and electrons. Products and remaining precursor ions aretransferred back for detection using the orbitrap analyzer 510 byswitching the DC potentials 526 to optimize the axial kinetic energy ofthe ions and maximize capturing efficiency in the ejection trap 507.

In this example of a processing cycle 523, the potential energy of theions is switched between three different levels in segment 517. The DCpotential applied during injection into the LQIT 501 is configured tomatch the DC potential applied to the ejection trap 507 to avoidcollisional activation in the hexapole 511 by keeping axial ion energybelow 10eV. Controlling the interaction energy in ion-ion orion-electron activation dissociation experiments requires the DCpotential applied to segment 517 to be adjusted relative to the kineticenergy of the incoming ions or electrons. Finally, detection of productsspecies using the orbitrap 510 requires ions to be released from a newDC electrical potential level to ensure efficient trapping in theejection trap 507.

Yet another exemplary embodiment of the present invention is shown inFIG. 6. The schematic diagram of the instrument 600 shows the segmentedLQIT 501 attached to a mass spectrometric platform 502 whichincorporates an orbitrap mass analyzer 510. An additional bridginghexapole ion guide 623 and a DC lens electrode 624 are disposed betweenthe LQIT and the original ion guide 511 to provide an additional pumpingregion to reduce the gas load to the orbitrap. The LQIT isdifferentially pumped and can accommodate heavier gas loads. Light gasessuch as molecular hydrogen or hydrogen radicals can be admitted to theLQIT at higher densities.

An example of a processing cycle 625 and the corresponding switchingsequence of the DC electrical potential profile is also presented inFIG. 6 where ions released from the ejection trap 507 or selected in theQMF 503 are transferred through the ion guide 511 and the bridginghexapole 623 into the LQIT 501 and stored in segment 517. The energy ofthe interaction between ions and externally injected electrons iscontrolled by adjusting the DC electrical potential of the trappingregion to a single or multiple levels. In this example a third trappingregion is formed by adjusting the DC field components in segments 519,520 and 521 for storing and accumulating ions. Following theactivation-dissociation step 626 performed in the second trapping regionin segment 517 the potential energy of the ions is raised slightly abovethe DC potential level of segment 520. Products and remaining precursorions are transferred with minimum kinetic energy by switching the DCpotentials applied to segments 516, 517 and 518, as shown in step 627.The potentials applied to segments 519, 520 and 521 are preferably fixedwhile the DC potential profile of the remaining segments is adjusted tothe original settings 628 to receive a second pulse of ions. Steps 626,627 and 628 can be repeated until a satisfactory number of product ionshave been produced to improve signal-to-noise ratio for low probabilityor low efficiency dissociation pathways. In this example, followingtransfer of ions to the third trapping region as shown in step 627 thereare two possible options. The first option is to switch the DC potentialas shown in step 629 to send product ions back to the ejection trap formass analysis using the orbitrap. The second option is to transfer ionsin the first trapping region for ion isolation and slow heating CID asshown in step 630. Finally, ions are released back to the ejection trap507 by switching the DC potentials applied to segment 513 and lenselectrode 624 as shown in step 631.

Another DC potential profile sequence 725 for multiple-stageactivation-dissociation experiments performed on the LQIT platform ofFIG. 6 is shown in FIG. 7. The DC potentials originally applied to thesegments 726 are set to transfer ions to the first trapping region insegment 514 for ion isolation and slow heating CID. It is also desirableto select a single m/z ratio or multiple m/z ratios CID product ions byperforming a second isolation step in segment 514. Segments 515-518 aresubsequently switched 727 to transfer selected CID products to thesecond trapping region in segment 517 where control of the ion potentialenergy based on the methods disclosed in the present invention isexercised to activate and dissociate ions using externally injectedelectrons. Second generation products are preferably parked in the thirdtrapping region in segment 520 by adjusting the level of the DCelectrical potentials of to potential well and switching the DC fieldcomponents applied to segments 518, 519 as shown in step 728. The DCprofile can be relaxed to the original settings as shown in step 729 toreceive a new pulse of ions repeating the processing cycle to accumulatesecond generation products and improve signal-to-noise ratio during massanalysis. Third generation products can be produced by transferring ionsfrom the third to the first trapping region as shown in step 730.Finally, third generation products are sent back to the ejection trap byswitching DC potentials to establish a weak DC gradient to maintain ionkinetic energy below 5 eV.

In processing step 727, the second trapping region is populated withions and adjusting the DC field components to different levels alsoalters the potential energy of the ions. Transitions of the DC potentialprofile can also be performed in regions where ions are not present, asshown for example in processing step 730 where the energy level of thesecond trapping region is raised to transfer ions between trappingregions under the influence of a weak DC gradient. In another preferredmode of operation efficient transfer is also possible by dropping thepotential energy of the ions accumulated in the third trapping regionclose to the potential level of the second trapping region. Differenttransitions of the DC field components of the LQIT can be exercised toperform the same processing steps afforded by the highly flexibleelectronics circuitry of the present invention disclosed in FIG. 3.

Yet another processing cycle 825 for multiple-stageactivation-dissociation experiments performed on the LQIT platform ofFIG. 6 and assisted by potential energy control of the ions is shown inFIG. 8. The DC potentials originally applied to the segments 826 are setto transfer ions to the second trapping region in segment 517 for ionactivation using externally injected electrons. Preferably, thepotential energy of product ions is dropped prior to switchingpotentials for transfer. The second processing step 827 involves liftingthe potential energy and transferring ions to a neighboring trappingregion simultaneously. The lift-transfer method minimizes the energyimparted to ions in collisions with background gas molecules and alsominimizes the time required for cooling ions before the next processingstep is applied. Faster transitions between processing steps aretherefore accomplished reducing the overall time of the processingcycle. In this example of a processing cycle, first generation productions stored in the first trapping region in segment 514 are processedusing isolation waveforms and selected m/z ratios are released back tothe ejection trap 828. The DC potentials applied to the RF ion guides511 and 623 are dropped and ions released axially from the ejection trapundergo energetic collisions with background gas molecules to formsecond generation high-energy CID products, which are decelerated in theLQIT in the presence of a RF trapping field and a reflecting DC fieldproduced by adjusting the DC field components as shown in step 829.Switching the DC potential applied to segment 513 prevents energeticions from escaping the LQIT and ions are thermalized in the firsttrapping region. The potential energy of the ions is raised again 830and DC potentials are switched 831 to transfer ions to the ejection trapfor mass analysis.

The foregoing discussion discloses and describes exemplary methods,electronics circuitries and embodiments of the present invention. Aswill be understood by those familiar with the art, the invention may beembodied in other specific forms without departing from the spirit oressential characteristics thereof.

For example, the linear ion trap of the present invention can also beconfigured to accommodate surface induced dissociation experiments byaccelerating molecular ions with sufficiently high kinetic energiestoward an end-cap electrode positioned at the far end of the linear iontrap and partly immersed in the RF trapping field of a trapping region.Simultaneous switching the DC field components in neighboring segmentsis preferably applied to store fragment ions therein. Acceleration tohigh kinetic energies is accomplished by high voltage DC switchingapplied to the end-cap electrode or to a trap segment. The surfaceinduced dissociation technique can be applied independently or in serieswith other processing techniques as disclosed in the present invention.

In another example, ions stored in a trapping region of the linear iontrap are ejected into an ion mobility spectrometer for separation basedon cross section and charge state. Mobility separated ions can beselected using a gate and transferred back to the linear ion trap forfurther processing. Transferring ions to the linear ion trap requireslifting the DC electrical potential across the trapping region of theion mobility spectrometer and switching one or more DC field componentsforming the trapping region to release ions backwards, similarly to themethodology disclosed in the present invention. The method also requiresapplying a RF field component for radial confinement of the ions in thetrapping region and also reversing the DC gradient across the ionmobility spectrometer.

Accordingly, the disclosure of the present invention is intended to beillustrative, but not limiting, of the scope of the invention, which isset forth in the following claims.

What is claimed is:
 1. A linear ion trap system comprising: a linear iontrap having at least two discrete trapping regions for processing ions;an RF electrical potential generator for producing two RF waveforms,each applied to a pair of pole electrodes of the linear ion trap forminga RF trapping field component to trap ions radially; a multi-output DCelectrical potential generator for producing a first set of multiple DCfield components superimposed to the RF trapping field component anddistributed across the length of the linear ion trap to control ionsaxially; and a control unit configured to switch the DC electricalpotentials and corresponding DC field components collectively forming afirst trapping region of the at least two discrete trapping regions thatis populated with ions to alter ion potential energy from a first levelto a second level, and to enable at least a first ion processing step inat least one of the first and second levels.
 2. The linear ion trapsystem of claim 1, wherein the control unit is further configured toswitch at least a portion of the DC electrical potentials andcorresponding DC field components collectively to transfer processedions away from the linear ion trap.
 3. The linear ion trap system ofclaim 2, wherein the linear ion trap is configured for connection inseries to an ion mobility spectrometer that receives and separates ionsprocessed in the linear ion trap.
 4. The linear ion trap system of claim3, wherein the control unit is further configured to switch at least aportion of a second set of multiple DC field components distributedacross the length of the ion mobility spectrometer to enable theprocesses of receiving and separating ions by the ion mobilityspectrometer.
 5. The linear ion trap system of claim 4, wherein thecontrol unit is further configured to drive a gate for selecting aportion of the mobility separated ions.
 6. The linear ion trap system ofclaim 5, further comprising another RF electrical potential generatorfor producing two additional RF waveforms, each applied to electrodes ofthe ion mobility spectrometer forming a corresponding RF trapping fieldcomponent, to enable trapping of the selected portion of mobilityseparated ions in the ion mobility spectrometer.
 7. The linear ion trapsystem of claim 6, wherein the control unit is further configured tolift the potential energy of trapped ions selected by the gate and tofurther switch at least one DC field component of the ion mobilityspectrometer to enable transfer of selected ions back to the linear iontrap.
 8. The linear ion trap system of claim 1, wherein the linear iontrap has an end-cap electrode positioned at one end of the linear iontrap.
 9. The linear ion trap system of claim 8, wherein a high voltageDC switch is connected to the end-cap electrode of the linear ion trapfor producing and applying a high voltage pulse.
 10. The linear ion trapsystem of claim 9, wherein the control unit is further configured toswitch at least a portion of the DC electrical potentials andcorresponding DC field components collectively and further configured tocontrol the high voltage DC switch to accelerate the ions toward theend-cap electrode to induce surface dissociation of the ions.
 11. Thelinear ion trap system of claim 10, further comprising at least one gaspulse valve for applying pulses of gas to dynamically control pressurein the linear ion trap during surface induced dissociation.
 12. Thelinear ion trap system of claim 11, wherein the control unit is furtherconfigured to switch the DC field components in a neighboring segment ofthe end-cap electrode to facilitate storage of fragment ions produced bysurface induced dissociation.
 13. A linear ion trap system comprising:at least two discrete trapping regions for processing ions; an RFelectrical potential generator for producing two RF waveforms, eachapplied to a pair of pole electrodes of the linear ion trap forming a RFtrapping field component to trap ions radially; a multi-output DCelectrical potential generator for producing multiple DC fieldcomponents superimposed to the RF trapping field component anddistributed across the length of the linear ion trap to control ionsaxially; an end-cap electrode positioned at an end of the linear iontrap; a high voltage DC switch for producing and applying a high voltagepulse to the end-cap electrode; and a control unit configured to switchthe DC electrical potentials and corresponding DC field componentscollectively and to drive the high voltage DC switch to acceleratemovement of the ions toward the end-cap electrode to induce surfacedissociation of the ions.
 14. The linear ion trap system of claim 13,further comprising at least one gas pulse valve for applying pulses ofgas to dynamically control pressure in the linear ion trap duringsurface induced dissociation.
 15. A mass spectrometer comprising: alinear ion trap having at least one discrete trapping region forprocessing ions; a first RF electrical potential generator for producingtwo RF waveforms, each applied to a pair of pole electrodes of thelinear ion trap forming a first RF trapping field component to trap ionsradially; an ion mobility spectrometer disposed in series with thelinear ion trap and arranged for receiving and separating ions processedin the linear ion trap and for separating and selecting processed ionsusing a gate; a second RF electrical potential generator for producingtwo RF waveforms, each applied to electrodes of the ion mobilityspectrometer forming a second RF trapping field component to trap theselected processed ions radially; a multi-output DC electrical potentialgenerator for producing a first set of multiple DC field componentssuperimposed to the first RF trapping field component and distributedacross the length of the linear ion trap to control ions axially and forproducing a second set of multiple DC field components distributedacross the length of the ion mobility spectrometer; and a control unitconfigured to switch DC electrical potentials and corresponding DC fieldcomponents collectively of the ion mobility spectrometer to transferback to the linear ion trap the processed ions selected by the gate ofthe ion mobility spectrometer.
 16. The mass spectrometer of claim 15,wherein the control unit is configured to transfer ions back to thelinear ion trap by lifting the potential energy of the ions in the ionmobility spectrometer.
 17. A method for processing ions in a linear iontrap defining a trapping field, the method comprising: trapping ions inthe trapping field of the linear ion trap produced by the superpositionof a RF trapping field component for radial confinement of the ions andmultiple DC field components for axial control of the ions; distributingthe multiple DC field components spatially along the axis of the linearion trap to form at least two discrete trapping regions of the linearion trap; subjecting ions in a first of the at least two discretetrapping regions at at least a first potential energy level to at leasta first processing step; and altering ion potential energy by switchingat least a portion of the multiple DC field components collectively tofacilitate further processing of ions.
 18. The method of claim 17,further comprising receiving and separating ions processed in the linearion trap by an ion mobility spectrometer connected in series to thelinear ion trap.
 19. The method of claim 18, further comprisingselecting a portion of the mobility separated ions and transferring theselected portion of the mobility separated ions back to the linear iontrap for further processing.
 20. The method of claim 19, wherein thetransferring of the selected portion of the mobility separated ions backto the linear ion trap comprises lifting a DC electrical potentialacross a trapping region of the ion mobility spectrometer and switchingat least one DC field component of the ion mobility spectrometer toenable transfer of the selected portion of the mobility separated ionsback to the linear ion trap.